The goal of this research proposal is to synthesize the biologically active xenicane small molecule natural products in order to facilitate further research to understand the biology of cancer and bacterial diseases. A significant number of anticancer and antibacterial drugs have been developed over the past twenty years primarily due to the studies of small molecule natural products (SMNPs). Owing to the paucity of material from non-renewable, slow-growing organisms the total chemical synthesis of SMNPs is required for rigorous biological evaluation. A short and concise synthetic route to a suite of structurally diverse and biologically active SMNPs would provide material for research to help understand the biology of diseases and determine new modalities for disease treatment. In this proposal a strategy that incorporates both a target- and diversity-oriented approach will be used to gain direct access to the semi-validated anticancer and antibacterial xenicane family tree of SMNPs. Key steps in this synthesis include Oppolzer hydroboration/transmetallation cyclization, dynamic kinetic resolution using the Shi epoxidation, Diels- Alder/retro Diels-Alder reaction, and titanium radical and Lewis acid mediated transannulations. Relevance of proposed research to public health: The biology of cancer and bacterial diseases is not yet fully understood. The synthesis and evaluation of new biologically active compounds is needed for drug development and determination of new methods for disease treatment. The synthetic route in this proposal would give access to a suite of bioactive natural products which can serve as tools to facilitate further research to understand the biology of cancer and bacterial diseases in an effort to advance modern medicine.